We will continue to investigate mechanisms of pulmonary oxygen toxicity and its prevention in the human newborn and in experimental animals. A human study of vitamin E influences in preventing or modifying the course of bronchopulmonary dysplasia will be extended to investigation of higher dose vitamin E treatment. Antioxidant influences will be assessed by clinical and radiographic criteria and other indices of oxygen and antioxidant influences will include red cell stability and lipid composition, serum concentrations of vitamin E and quality of phospholipids in tracheal aspirates. We will continue to follow infants for development of retrolental fibroplasia. Animal studies will utilize newborn rabbits and guinea pigs, species with different sensitivities to oxygen toxicity. We will compare different antioxidants (vitamin E, ascorbate, beta-carotene) in modifying the endogenous antioxidants responses. This includes effects on antioxidant enzymes (superoxide dismutase, catalse, glutathione reductase and peroxidase) and on levels of glutathione. Quantitative morphometry will be carried out and morphological studies will be done by light and electron microscopy. The effects of high and low amounts of polyunsaturated fatty acids in the diet and absolute deficiency of vitamin E will also be investigated. We will also examine influences of oxygen and antioxidants on lung metabolism and on surfactant phospholipid synthesis during the acute phase of injury and recovery. Investigation of endogenous antioxidant defenses, cellular metabolism and phospholipid synthesis in isolated type II cells exposed to hyperoxic stress will be an important extension of current studies.